July 3, 2014

Whitehead Institute scientists and associates have modified red blood cells (RBCs) to carry a range of valuable therapeutic and diagnostic payloads — such as drugs, vaccines, and disease-detecting imaging agents — for delivery to specific sites throughout the body.

“We wanted to create high-value red cells that do more than simply carry oxygen,” says Whitehead Founding Member Harvey Lodish, who collaborated with Whitehead Member Hidde Ploegh in this pursuit. So they modified the genes and enzymes in mouse and human RBCs in culture (in the lab).

The work, published this week in the Proceedings of the National Academy of Sciences (PNAS), combines Lodish’s expertise in the biology of red blood cells (RBCs) with biochemical methods developed in Ploegh’s lab.

RBCs are an attractive vehicle for potential therapeutic applications, the researchers say. They are more numerous than any other cell type in the body. They have a long lifespan (up to 120 days in circulation). And during RBC production, the progenitor cells that eventually mature to become RBCs jettison their nuclei and all DNA. Without a nucleus, a mature RBC lacks any genetic material or any signs of earlier genetic manipulation that could result in tumor formation or other adverse effects.*

Wide range of medical uses

The researchers suggest that the applications are potentially vast, including:

Suppress the unwanted immune response that often accompanies treatment with protein-based therapies.

Neutralize a toxin. “Because the modified human red blood cells can circulate in the body for up to four months, one could envision a scenario in which the cells are used to introduce antibodies that neutralize a toxin,” says Ploegh. “The result would be long-lasting reserves of antitoxin antibodies.” That’s why the U.S. military and its Defense Advanced Research Projects Agency (DARPA) is supporting the research at Whitehead in the interest of developing treatments or vaccines effective against biological weapons.

* Exploiting this feature, Lodish and his lab introduced genes coding for specific slightly modified normal red cell surface proteins into early-stage RBC progenitors. As the RBCs approach maturity and enucleate, the proteins remain on the cell surface, where they are modified by Ploegh’s protein-labeling technique. This approach, called “sortagging,” relies on the bacterial enzyme sortase A to establish a strong chemical bond between the surface protein and a substance of choice, be it a small-molecule therapeutic or an antibody capable of binding a toxin. The modifications leave the cells and their surfaces unharmed.

Abstract of Proceedings of the National Academy of Sciences paper

We developed modified RBCs to serve as carriers for systemic delivery of a wide array of payloads. These RBCs contain modified proteins on their plasma membrane, which can be labeled in a sortase-catalyzed reaction under native conditions without inflicting damage to the target membrane or cell. Sortase accommodates a wide range of natural and synthetic payloads that allow modification of RBCs with substituents that cannot be encoded genetically. As proof of principle, we demonstrate site-specific conjugation of biotin to in vitro-differentiated mouse erythroblasts as well as to mature mouse RBCs. Thus modified, RBCs remain in the bloodstream for up to 28 d. A single domain antibody attached enzymatically to RBCs enables them to bind specifically to target cells that express the antibody target. We extend these experiments to human RBCs and demonstrate efficient sortase-mediated labeling of in vitro-differentiated human reticulocytes.

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I like the concept for this research as well. It is one thing to enhance the absorption, storage, and release of oxygen and carbon dioxide – e.g., as Ray Kurzweil has predicted. It is another to utilize the particular properties of red blood cells for access, detection, and delivery of other important things. Nanobots in the bloodstream would be far smaller than red blood cells, but for now, the RBC themselves seem just fine to work with.

Ha, that would seem a bit like magic … add a drop of blood from this special kind of toad, sprinkle in the pollen from this rare plant whose leaves fluoresce at night, and a miracle nano-tattoo (that connects to wi-fi) peels off the glass plate …..

That is why so many SF magazine editors tell their writers not to project too much nanotech into the future…it seems too much like magic, asiwel.

But it won’t be long before your I-phone comes as a caplet of nanoes that you swallow. They will find the right place and the antenna will migrate to where your neck meets your head and appear as a broadband tattoo just beneath your left earlobe.

It will be an outline of a Delicious apple, unless you pay extra for some Lucky Charms.

Ha! Doesn’t that sound like the truth. Economics 3.0 … with an emergent “mark of the Apple” bio-logo, to boot. Next crusade pits the Apple versus the Google and/or the fierce but decadent MS, while the Linux silent majority quiver in the crowd-ed wings of a virtual reality.

(Actually, we already had this history lesson in the halls of academia in the 1980′s when the great PC melting pot congealed into once-again-private offices of Wang, Atari, Apple II, and IBM PC (converted) people .. with occasional DECs & Primes & Data Generals trying to regain social control.)

Why, Gordon! When did you become so ideologically pure? .. sounding like a regular new convert. LINUX? No doubt it is pretty darn good and crowd-sourced, etc. (and among dozens I too have used to good effect). But I’m more pragmatic .. and the cost of learning “new” development platforms is becoming prohibitive (or not worth it) more and more in “old age.” Sometimes it is much easier to stick with what you know than to make every task into a start-up cycle. But that is a bit different from the 1980′s PC wars … where each party seemed to insist that everybody should convert to his/her “chosen OS.” :-} (Why imagine if we lived in a 7-bit Wang world .. or still used Roman numerals!)

I love ya’ asiwel…but I’m not being ideologically pure. I have just studied enough history to see that the self-replicating robots must belong to everybody. They can quarry mountains to build the islands that support all of the desalination plants to turn all of the deserts green if they are not owned by a new start-up billionaire.

If these robots throw all of the people out of work without paying the taxes that support the people…then those people who own all of those 300 million guns will start shooting down all of those robots along with all of those Wall Streeters who own them.

This will lead to such a bloody civil war that the consequences are unimaginable.

No, the consequences of such a “war” are NOT unimaginable…If the Top 1% control the technology and decided to go to war with the other 99%, it would be GENOCIDE–they would SLAUGHTER the other 99% in a matter of DAYs if all they had to defend themselves were today’s firearms.

Numbers do not matter–with surveillance drones to map enemy locations, using X-Ray, T-Ray, and Sonar to find underground bases, long range “smart” artillery to take them out, and intelligent swarms of micro-drones to hunt down individuals–all made from graphene super-polymers or alloys–they would easily wipe out 3-400 million people armed only with pop-guns.

Ah, on a more serious note, yes and no. (I just finished the Coursera MOOC from Princeton on the “Paradoxes of War” and highly recommend it for considering how things may change in the 21st century.) The consequences ARE imaginable .. and they certainly are not good. But in a trans-nationalistic, .01% feudalistic society with international corporations-that-are-people, etc., there is not likely to be a clear-cut “us” and “them.” In fact, “they” might almost certainly spend more energy and effort fighting among themselves. The technology you mention may not help the overlords, unless it can truly “find” the various “enemies” in order to “slaughter” them. Likewise, those masses may be armed with a variety of options and tools that do not resemble “pop-guns.” Funny thing is that Gordon’s suggested path to the future – essentially empowering everybody – may be the most radical and least predictable of all possible futures. Olympus, Asgard, Heaven and Hell, or Vyahrtis and Paatalas may not be exactly the most democratic places to be living in :-}